Prognostic impact of CEBPA bZIP domain mutation in acute myeloid leukemia

被引：75

作者：

Wakita, Satoshi ^{[1
]}

Sakaguchi, Masahiro ^{[1
]}

Oh, Iekuni ^{[2
]}

Kako, Shinichi ^{[3
]}

Toya, Takashi ^{[4
]}

Najima, Yuho ^{[4
]}

Doki, Noriko ^{[4
]}

Kanda, Junya ^{[5
]}

Kuroda, Junya ^{[6
]}

Mori, Shinichiro ^{[7
]}

Satake, Atsushi ^{[8
]}

Usuki, Kensuke ^{[9
]}

Ueki, Toshimitsu ^{[10
]}

Uoshima, Nobuhiko ^{[11
]}

Kobayashi, Yutaka ^{[11
]}

Kawata, Eri ^{[12
]}

Tajika, Kenji ^{[13
]}

Nagao, Yuhei ^{[14
]}

Shono, Katsuhiro ^{[14
]}

Shibusawa, Motoharu ^{[15
]}

Tadokoro, Jiro ^{[15
]}

Kayamori, Kensuke ^{[16
]}

Hagihara, Masao ^{[17
]}

Uchiyama, Hitoji ^{[18
]}

Uchida, Naoyuki ^{[19
]}

Kubota, Yasushi ^{[20
]}

Kimura, Shinya ^{[20
]}

Nagoshi, Hisao ^{[21
]}

Ichinohe, Tatsuo ^{[21
]}

Kurosawa, Saiko ^{[22
]}

Motomura, Sayuri ^{[23
]}

Hashimoto, Akiko ^{[24
]}

Muto, Hideharu ^{[25
]}

Sato, Eriko ^{[26
]}

Ogata, Masao ^{[27
]}

Mitsuhashi, Kenjiro ^{[28
]}

Ando, Jun ^{[29
]}

Marumo, Atsushi ^{[1
]}

Omori, Ikuko ^{[1
]}

Fujiwara, Yusuke ^{[1
]}

Terada, Kazuki ^{[1
]}

Yui, Shunsuke ^{[1
]}

Arai, Kunihito ^{[1
]}

Kitano, Tomoaki ^{[1
]}

Miyata, Miho ^{[1
]}

Kurosawa, Akiyo ^{[1
]}

Mizoguchi, Ayumi ^{[1
]}

Komatsu, Norio ^{[29
]}

Fukuda, Takahiro ^{[22
]}

Ohashi, Kazuteru ^{[4
]}

机构：

[1] Nippon Med Sch, Dept Hematol, Tokyo, Japan

[2] Jichi Med Univ, Dept Med, Div Hematol, Shimotsuke, Tochigi, Japan

[3] Jichi Med Univ Saitama Med Ctr, Div Hematol, Saitama, Japan

[4] Komagome Hosp, Tokyo Metropolitan Canc & Infect Dis Ctr, Hematol Div, Tokyo, Japan

[5] Kyoto Univ, Grad Sch Med, Dept Hematol & Oncol, Kyoto, Japan

[6] Kyoto Prefectural Univ Med, Div Hematol & Oncol, Kyoto, Japan

[7] St Lukes Int Hosp, Hematooncol Dept, Tokyo, Japan

[8] Kansai Med Univ, Dept Internal Med 1, Osaka, Japan

[9] NTT Med Ctr Tokyo, Dept Hematol, Tokyo, Japan

[10] Nagano Red Cross Hosp, Dept Hematol, Nagano, Japan

[11] Kyoto Daini Hosp, Dept Hematol, Japanese Red Cross, Kyoto, Japan

[12] Matsushita Mem Hosp, Dept Hematol, Osaka, Japan

[13] Yokohama Minami Kyousai Hosp, Dept Hematol, Yokohama, Kanagawa, Japan

[14] Chiba Aoba Municipal Hosp, Dept Hematol, Chiba, Japan

[15] IMS Grp Shinmatsudo Cent Gen Hosp, Dept Hematol, Chiba, Japan

[16] Chiba Univ Hosp, Dept Hematol, Chiba, Japan

[17] Eiju Gen Hop, Dept Hematol, Tokyo, Japan

[18] Japanese Red Cross Kyoto Daiichi Hosp, Dept Hematol, Kyoto, Japan

[19] Toranomon Gen Hosp, Dept Hematol, Federat Natl Publ Serv Personnel Mutual Aid Assoc, Tokyo, Japan

[20] Saga Univ, Fac Med, Dept Internal Med, Div Hematol Resp Med & Oncol, Saga, Japan

[21] Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Hematol & Oncol, Hiroshima, Japan

[22] Natl Canc Ctr, Dept Hematopoiet Stem Cell Transplantat, Tokyo, Japan

[23] Tokyo Metropolitan Hlth & Med Treatment Corp, Dept Hematol, Tama Hokubu Med Ctr, Tokyo, Japan

[24] Kobe City Nishi Kobe Med Ctr, Dept Immunol & Hematol, Kobe, Hyogo, Japan

[25] Tokyo Metropolitan Otsuka Hosp, Div Hematol, Tokyo, Japan

[26] Juntendo Univ, Dept Hematol, Nerima Hosp, Tokyo, Japan

[27] Oita Univ Hosp, Dept Hematol, Oita, Japan

[28] Saitama Red Cross Hosp, Dept Hematol, Saitama, Japan

[29] Juntendo Univ, Dept Hematol, Sch Med, Tokyo, Japan

来源：

BLOOD ADVANCES | 2022年 / 6卷 / 01期

关键词：

C/EBP-ALPHA; CELL TRANSPLANTATION; EXPRESSION; AML; DIAGNOSIS; FLT3-ITD; DISTINCT; RELAPSE; ASSAY;

D O I：

10.1182/bloodadvances.2021004292

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Mutations of CCAAT/enhancer-binding protein alpha (CEBPAmu) are found in 10% to 15% of de novo acute myeloid leukemia (AML) cases. Double-mutated CEBPA (CEBPAdm) is associated with a favorable prognosis; however, single-mutated CEBPA (CEBPAsm) does not seem to improve prognosis. We investigated CEBPAmu for prognosis in 1028 patients with AML, registered in the Multi-center Collaborative Program for Gene Sequencing of Japanese AML. It was found that CEBPAmu in the basic leucine zipper domain (bZIP) was strongly associated with a favorable prognosis, but CEBPAmu out of the bZIP domain was not. The presence of CEBPAmu in bZIP was a strong indicator of a higher chance of achieving complete remission (P < .001), better overall survival (OS; P < .001) and a lower risk of relapse (P < .001). The prognostic significance of CEBPAmu in bZIP was also observed in the subgroup with CEBPAsm (all patients: OS, P = .008; the cumulative incidence of relapse, P = .063; patients aged <_70 years and with intermediate-risk karyotype: OS, P = .008; cumulative incidence of relapse, P = .026). Multivariate analysis of 744 patients aged <_70 years showed that CEBPAmu in bZIP was the most potent predictor of OS (hazard ratio, 0.3287; P < .001). CEBPAdm was validated as a cofounding factor, which was overlapping with CEBPAmu in bZIP. In summary, these findings indicate that CEBPAmu in bZIP is a potent marker for AML prognosis. It holds potential in the refinement of treatment stratification and the develop-ment of targeted therapeutic approaches in CEBPA-mutated AML.

引用

页码：238 / 247

页数：10

共 21 条

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